Enable importing of SBML models into Chaste

[kwabenantim]

Background

• SBML and CellML are now widely adopted for defining and sharing models of subcellular biological processes.
• @MauriceHendrix and @mirams have developed chaste-codegen as a Python 3 replacement for Chaste’s CellML-to-Chaste-C++ converter.
• Other preliminary work by @jmosborne has investigated using libSBML to parse SBML files and create Chaste-compatible C++ classes specifying subcellular reaction networks (SBMLChaste).

Scope of Work Building on these efforts, we will:

• Extend the primary Chaste codebase to enable all users to import new/existing SBML models for gene regulatory networks and signalling pathways.
• Seek to validate these SBML capabilities through external compliance testing (https://synonym.caltech.edu/software/sbml-test-suite).

[kwabenantim]

Roadmap

• [ ] SRN Models
  • [x] Start with existing code from SBMLChaste.
    • [x] Check that existing code works with current Chaste develop.
    • [x] Check that existing code generator works with Python 3.
  • [ ] No cell-cell communication:
    • [x] Generate C++ Chaste code for simpler models that do not need cell-cell coupling e.g. Goldbeter (1991).
    • [ ] Add tests to check that generated model matches expected model.
    • [x] Check that generated models pass existing Chaste tests.
  • [ ] Cell-cell communication:
    • [ ] Generate C++ Chaste code for models that require cell-cell coupling e.g. Van Leeuwen (2007).
    • [ ] Add tests to check that generated model matches expected model.
    • [ ] Check that generated models pass existing Chaste tests.
• [ ] Cell-Cycle Models
  • [ ] Generate cell-cycle models from SBML for models that already exist in Chaste e.g. WntCellCycleModel.
    • [ ] Work out how to handle events (this isn't a consideration for SRN models).
      • [ ] Try using CVODE root finding to look for ODE events e.g. cell size drops to 0.
  • [ ] Add tests to check that generated model matches expected model.
  • [ ] Check that generated models pass existing Chaste tests.
• [ ] Project
  • [x] Create a separate chaste_codegen_sbml project.
  • [x] Pin specific versions of libSBML and other dependencies.
  • [ ] Use similar test setup as chaste_codegen i.e. use CMake to create a virtualenv etc.
    • [x] Use same virtualenv as chaste_codegen to avoid slowing down configuration.
    • [ ] Consider merging chaste_codegen_sbml and chaste_codegen into same package, perhaps one package with two submodules, one for cellml and the other for sbml.
  • [ ] Allow run-time / compile-time code generation from Chaste, similar to approach used in chaste_codegen.

Other

• [ ] Update https://en.wikipedia.org/wiki/List_of_systems_biology_modeling_software

[kwabenantim]

Goldbeter (1991)

• Paper: A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase
• SBML: https://www.ebi.ac.uk/biomodels/BIOMD0000000003
• Chaste Implementation:
  • Goldbeter1991OdeSystem cpp hpp
  • Goldbeter1991SrnModel cpp hpp

Notes

• Chaste C++ model was generated successfully from SBML using SBMLChaste.
• There are some differences in implementation between the generated model and the existing Chaste model.
• Current tests do not work for generated model due to implementation differences. For example:
  • Missing expected GetC(), GetM(), and GetX() methods to return state variables.
  • OdeSystem and SrnModel are combined in a single file in the generated model but separated in the original Chaste implementation.
  • Some code that needs fixing e.g. double activation of cdc2 kinase = cell * (1 + -1 * CDC-2 Kinase) * V1 * pow(K1 + -1 * CDC-2 Kinase + 1, -1);

Tests

• [x] TestGoldbeter1991CellSrn
  • Fix variable names.
  • Fix generated ODE number of parameters from 5 to 3.
  • Add methods to get state variables. Use variable names for clarity.
  • Disable "timescale conversions".
  • SetDt(0.1)
  • Use the RungeKutta4IvpOdeSolver solver, same as the existing class.
• [x] TestGoldbeter1991OdeSystem
• [x] TestGoldbeter1991OdeBasedSrnModels
  • Model identifier is "SbmlSrnWrapperModel-GoldbeterOdeSystem-3".

[mirams]

I would think GetM() etc. methods should be replaced by ones that follow the OdeSystemInformation form, e.g. GetVariable("M") or GetParameter("M") etc. (automatically available when OdeSystemInformation in the hpp is complete.)

[mirams]

Work is in a separate chaste_codegen_sbml project.